Patient characteristics and eligibility for biologics in severe asthma: Results from the Greek cohort of the RECOGNISE "real world" study.

BACKGROUND: Some patients with severe asthma do not achieve sufficient symptom control despite guideline-based treatment, and therefore receive oral (OCS) and systemic corticosteroids (SCS) on regular basis. The side effects of corticosteroid use negatively impact patients' health-related quality of life (HRQoL) and increase the disease burden. Biologics have shown promise in asthma therapy; however, identifying patients who might benefit from biologic therapy is complex due to the heterogeneous pathophysiology of the disease. METHODS: The European, non-interventional, multicentre RECOGNISE study (NCT03629782) assessed patient characteristics, asthma medication and control, HRQoL as assessed by St. George's Respiratory Questionnaire (SGRQ), and health care resource use in patients with severe asthma, as well as their eligibility for biologic treatment. Here, data from the Greek cohort (N = 97) are reported. RESULTS: In Greece, patients with severe asthma were more often female (71%) and never smokers (68%). 87% of patients were assessed as eligible for biologic treatment by investigator's judgement (per label criteria: 76%). Most patients had been previously treated with SCS (82% eligible vs 85% non-eligible), with OCS use being more common in non-eligible patients (23.1% vs 11.9%). More eligible patients had poorly controlled asthma (76% vs 54%), and more impaired HRQoL (mean total SGRQ score: 46% vs 39%); symptom burden was significantly higher (mean symptom score: 60% vs. 44%, p: 0.0389). CONCLUSIONS: A high proportion of Greek patients with severe asthma are eligible for biologic therapy; however, individual risk factors and differences between asthma types must be considered before the introduction of targeted therapy.

Weaning Failure in Critically Ill Patients Is Related to the Persistence of Sepsis Inflammation.

INTRODUCTION: Septic patients undergoing mechanical ventilation (MV) often experience difficulty in weaning. Th aim of this study was to determine whether inflammatory biomarkers of sepsis could be indicative of the failure or success of spontaneous breathing trial (SBT) in these patients. METHODS: Sixty-five patients on MV (42 septic and 23 intubated for other reasons) fulfilling the criteria for SBT were included in the study. Blood samples were collected right before, at the end of (30 min) and 24 h after the SBT. Serum inflammatory mediators associated with sepsis (IL-18, IL-18BP, TNF) were determined and correlated with the outcome of SBT. RESULTS: A successful SBT was achieved in 45 patients (69.2%). Septic patients had a higher percentage of SBT failure as compared to non-septic patients (85% vs. 15%, p = 0.026), with an odds ratio for failing 4.5 times (OR = 4.5 95%CI: 1.16-17.68, p 0.022). IL-18 levels and the relative mRNA expression in serum were significantly higher in septic as compared to non-septic patients (p < 0.05). Sepsis was independently associated with higher serum IL-18 and TNF levels in two time-point GEE models (53-723, p = 0.023 and 0.3-64, p = 0.048, respectively). IL-18BP displayed independent negative association with rapid shallow breathing index (RSBI) (95% CI: -17.6 to -4, p = 0.002). CONCLUSION: Sustained increased levels of IL-18 and IL-18BP, acknowledged markers of sepsis, were found to be indicative of SBT failure in patients recovering from sepsis. Our results show that, although subclinical, remaining septic inflammation that sustaines for a long time complicates the weaning procedure. Biomarkers for the estimation of the septic burden and the right time for weaning are needed.

Home-based maintenance tele-rehabilitation reduces the risk for acute exacerbations of COPD, hospitalisations and emergency department visits.

Pulmonary rehabilitation (PR) remains grossly underutilised by suitable patients worldwide. We investigated whether home-based maintenance tele-rehabilitation will be as effective as hospital-based maintenance rehabilitation and superior to usual care in reducing the risk for acute chronic obstructive pulmonary disease (COPD) exacerbations, hospitalisations and emergency department (ED) visits.Following completion of an initial 2-month PR programme this prospective, randomised controlled trial (between December 2013 and July 2015) compared 12 months of home-based maintenance tele-rehabilitation (n=47) with 12 months of hospital-based, outpatient, maintenance rehabilitation (n=50) and also to 12 months of usual care treatment (n=50) without initial PR.In a multivariate analysis during the 12-month follow-up, both home-based tele-rehabilitation and hospital-based PR remained independent predictors of a lower risk for 1) acute COPD exacerbation (incidence rate ratio (IRR) 0.517, 95% CI 0.389-0.687, and IRR 0.635, 95% CI 0.473-0.853), respectively, and 2) hospitalisations for acute COPD exacerbation (IRR 0.189, 95% CI 0.100-0.358, and IRR 0.375, 95% CI 0.207-0.681), respectively. However, only home-based maintenance tele-rehabilitation and not hospital-based, outpatient, maintenance PR was an independent predictor of ED visits (IRR 0.116, 95% CI 0.072-0.185).Home-based maintenance tele-rehabilitation is equally effective as hospital-based, outpatient, maintenance PR in reducing the risk for acute COPD exacerbation and hospitalisations. In addition, it encounters a lower risk for ED visits, thereby constituting a potentially effective alternative strategy to hospital-based, outpatient, maintenance PR.

Effect of pulmonary rehabilitation on tidal expiratory flow limitation at rest and during exercise in COPD patients.

We hypothesized that severe COPD patients who present with the disadvantageous phenomenon of Expiratory Flow Limitation (EFL) may benefit as COPD patients without EFL do after implementation of a Pulmonary Rehabilitation (PR) program. Forty-two stable COPD patients were studied at rest and during exercise. EFL and dynamic hyperinflation (DH) were documented using the negative expiratory pressure (NEP) technique and inspiratory capacity (IC) maneuvers, respectively. Patient centered outcomes were evaluated by the Saint-George's Respiratory Questionnaire (SGRQ) and the mMRC dyspnea scale. Before PR, 16 patients presented with EFL at rest and/or during exercise. After PR, EFL was abolished in 15 out of those 16 EFL patients who exhibited a significant increase in IC values. These were mainly accomplished through a modification of the breathing pattern. In the 26 NFL patients no increase was noted in their IC or a modification of their breathing pattern. However, both NFL and EFL COPD patients improved exercise capacity and patients centered outcomes undergoing the same PR program.

Acute effects of short term use of ecigarettes on Airways Physiology and Respiratory Symptoms in Smokers with and without Airway Obstructive Diseases and in Healthy non smokers.

BACKGROUND: Although the use of e-cigarettes is increasing worldwide, their short and long-term effects remain undefined. We aimed to study the acute effect of short-term use of e-cigarettes containing nicotine on lung function and respiratory symptoms in smokers with airways obstructive disease (COPD, asthma), "healthy" smokers, and healthy never smokers. METHODS: Respiratory symptoms, vital signs, exhaled NO, airway temperature, airway resistance (Raw), specific airway conductance (sGaw) and single nitrogen breath test were assessed before and immediately after short term use of an e-cigarette containing 11mg of nicotine among adults with COPD, asthma, "healthy" smokers, and never-smokers. The effect of the use of nicotine-free e-cigarettes among "healthy" never smokers was also studied. RESULTS: The majority of participants reported acute cough. Short term use of nicotine e-cigarettes was associated: a) with increased heart rate in all subjects except in the COPD group, b) decreased oxygen saturation in "healthy" and COPD smokers, c) increased Raw in asthmatic smokers, "healthy" smokers, and healthy never smokers, d) decreased sGaw in healthy subjects, and e) changed slope of phase III curve in asthmatic smokers. Short-term use of nicotine-free e-cigarettes increased Raw and decreased sGaw among healthy never smokers. CONCLUSIONS: Short-term use of an e-cigarette has acute effects on airways physiology and respiratory symptoms in COPD smokers, asthmatic smokers, "healthy" smokers and healthy never smokers. E-cigarette use was associated with effects in "healthy" never smokers irrespectively of nicotine concentration. More studies are needed to investigate both short and long-term effects of e-cigarette use.

Endobronchial Ultrasound Bronchoscopy to the Heart of the Matter.

Endobronchial ultrasound has been one of the success stories of the last decade, and the utility of the procedure continues to expand. Originally, it was developed for the staging and diagnosis of lung cancer, but its use rapidly expanded to other malignancies and even benign disease. We present the case of a patient originally referred with suspected endocarditis who was found to have a mass involving the right ventricle and the pulmonary outflow tract. Endobronchial ultrasound-guided biopsy was used to obtain a tissue diagnosis from the cardiac mass.

Impact of hemodialysis on dyspnea and lung function in end stage kidney disease patients.

BACKGROUND: Respiratory symptoms are usually underestimated in patients with chronic kidney disease undergoing maintenance hemodialysis. Therefore, we set out to investigate the prevalence of patients chronic dyspnea and the relationship of the symptom to lung function indices. METHODS: Twenty-five clinically stable hemodialysis patients were included. The mMRC dyspnea scale was applied before and after hemodialysis. Spirometry, single breath nitrogen test, arterial blood gases, static maximum inspiratory (P(imax)) and expiratory (P(emax)) muscle pressures, and mouth occlusion pressure (P 0.1) were also measured. RESULTS: Despite normal spirometry, all patients (100%) reported mild to moderate degree of chronic dyspnea pre which was reduced after hemodialysis. The sole predictor of (Δ) mMRC was the (Δ) P 0.1 (r = 0.71, P < 0.001). The P(imax) was reduced before and correlated with the duration of hemodialysis (r = 0.614, P < 0.001), whilst after the session it was significantly increased (P < 0.001). Finally (Δ) weight was correlated with the (Δ) P(imax) %pred (r = 0.533, P = 0,006) and with the (Δ) CV (%pred) (r = 0.65, P < 0.001). CONCLUSION: We conclude that dyspnea is the major symptom among the CKD patients that improves after hemodialysis. The neuromechanical dissociation observed probably is one of the major pathophysiologic mechanisms of dyspnea.

Dyspnea and respiratory muscle strength in end-stage liver disease.

AIM: To investigate the prevalence of chronic dyspnea and its relationship to respiratory muscle function in end-stage liver disease. METHODS: Sixty-eight consecutive, ambulatory, Caucasian patients with end-stage liver disease, candidates for liver transplantation, were referred for preoperative respiratory function assessment. Forty of these (29 men) were included in this preliminary study after applying strict inclusion and exclusion criteria. Seventeen of 40 patients (42%) had ascites, but none of them was cachectic. Fifteen of 40 patients (38%) had a history of hepatic encephalopathy, though none of them was symptomatic at study time. All patients with a known history and/or presence of co-morbidities were excluded. Chronic dyspnea was rated according to the modified medical research council (mMRC) 6-point scale. Liver disease severity was assessed according to the Model for end-stage liver disease (MELD). Routine lung function tests, maximum static expiratory (Pemax) and inspiratory (Pimax) mouth pressures were measured. Respiratory muscle strength (RMS) was calculated from Pimax and Pemax values. In addition, arterial blood gases and pattern of breathing (VE: minute ventilation; VT: tidal volume; VT/TI: mean inspiratory flow; TI: duration of inspiration) were measured. RESULTS: Thirty-five (88%) of 40 patients aged (mean ± SD) 52 ± 10 years reported various degrees of chronic dyspnea (mMRC), ranging from 0 to 4, with a mean value of 2.0 ± 1.2. MELD score was 14 ± 6. Pemax, percent of predicted (%pred) was 105 ± 35, Pimax, %pred was 90 ± 29, and RMS, %pred was 97 ± 30. These pressures were below the normal limits in 12 (30%), 15 (38%), and 14 (35%) patients, respectively. Furthermore, comparing the subgroups of ascites to non-ascites patients, all respiratory muscle indices measured were found significantly decreased in ascites patients. Patients with ascites also had a significantly worse MELD score compared to non-ascites ones (P = 0.006). Significant correlations were found between chronic dyspnea and respiratory muscle function indices in all patients. Specifically, mMRC score was significantly correlated with Pemax, Pimax, and RMS (r = -0.53, P < 0.001; r = -0.42, P < 0.01; r = -0.51, P < 0.001, respectively). These correlations were substantially closer in the non-ascites subgroup (r = -0.82, P < 0.0001; r = -0.61, P < 0.01; r = -0.79, P < 0.0001, respectively) compared to all patients. Similar results were found for the relationship between mMRC vs MELD score, and MELD score vs respiratory muscle strength indices. In all patients the sole predictor of mMRC score was RMS (r = -0.51, P < 0.001). In the subgroup of patients without ascites this relationship becomes closer (r = -0.79, P < 0.001), whilst this relationship breaks down in the subgroup of patients with ascites. The disappearance of such a correlation may be due to the fact that ascites acts as a "confounding" factor. PaCO2 (4.4 ± 0.5 kPa) was increased, whereas pH (7.49 ± 0.04) was decreased in 26 (65%) and 34 (85%) patients, respectively. PaO2 (12.3 ± 0.04 kPa) was within normal limits. VE (11.5 ± 3.5 L/min), VT (0.735 ± 0.287 L), and VT/TI (0.449±0.129 L/s) were increased signifying hyperventilation in both subgroups of patients. VT/TI was significantly higher in patients with ascites than without ascites. Significant correlations, albeit weak, were found for PaCO2 with VE and VT/TI (r = -0.44, P < 0.01; r = -0.41, P < 0.01, respectively). CONCLUSION: The prevalence of chronic dyspnea is 88% in end-stage liver disease. The mMRC score closely correlates with respiratory muscle strength.

Driving-Related Neuropsychological Performance in Stable COPD Patients.

Background. Cognitive deterioration may impair COPD patient's ability to perform tasks like driving vehicles. We investigated: (a) whether subclinical neuropsychological deficits occur in stable COPD patients with mild hypoxemia (PaO(2) > 55 mmHg), and (b) whether these deficits affect their driving performance. Methods. We recruited 35 stable COPD patients and 10 normal subjects matched for age, IQ, and level of education. All subjects underwent an attention/alertness battery of tests for assessing driving performance based on the Vienna Test System. Pulmonary function tests, arterial blood gases, and dyspnea severity were also recorded. Results. COPD patients performed significantly worse than normal subjects on tests suitable for evaluating driving ability. Therefore, many (22/35) COPD patients were classified as having inadequate driving ability (failure at least in one of the tests), whereas most (8/10) healthy individuals were classified as safe drivers (P = 0.029). PaO(2) and FEV1 were correlated with almost all neuropsychological tests. Conclusions. COPD patients should be warned of the potential danger and risk they face when they drive any kind of vehicle, even when they do not exhibit overt symptoms related to driving inability. This is due to the fact that stable COPD patients may manifest impaired information processing operations.

Methods for Assessing Expiratory Flow Limitation during Tidal Breathing in COPD Patients.

Patients with severe COPD often exhale along the same flow-volume curve during quite breathing as during forced expiratory vital capacity manoeuvre, and this has been taken as indicating expiratory flow limitation at rest (EFL(T)). Therefore, EFL(T), namely, attainment of maximal expiratory flow during tidal expiration, occurs when an increase in transpulmonary pressure causes no increase in expiratory flow. EFL(T) leads to small airway injury and promotes dynamic pulmonary hyperinflation with concurrent dyspnoea and exercise limitation. In fact, EFL(T) occurs commonly in COPD patients (mainly in GOLD III and IV stage) in whom the latter symptoms are common. The existing up-to-date physiological methods for assessing expiratory flow limitation (EFL(T)) are reviewed in the present work. Among the currently available techniques, the negative expiratory pressure (NEP) has been validated in a wide variety of settings and disorders. Consequently, it should be regarded as a simple, non invasive, most practical, and accurate new technique.

Pathophysiology of evolution of small airways disease to overt COPD.

BACKGROUND: The slope of phase III (single breath nitrogen test), an index of ventilation inhomogeneity, has been used for early detection of COPD. Tidal airway closure (cyclic opening and closure of the peripheral airways during tidal breathing; AC(T)) and expiratory flow limitation (attainment of maximal expiratory flow during tidal expiration; EFL(T)) cause small airways disease (SAD). The relationships of these indices with COPD severity may reflect the progress from SAD to overt COPD. METHODS: In this cross-sectional study we have assessed for the first time the phase III slope, AC(T) and EFL(T) in 10 smokers with normal spirometry (group O) and 40 COPD patients with GOLD scores from I to IV. RESULTS: In most group O smokers the phase III slope was increased, and further increased with GOLD severity (up to 800%pred in GOLD IV). A close correlation was found of slope with GOLD (r = 0.77). AC(T) was absent in smokers with normal spirometry and in most patients with mild COPD. EFL(T) first appeared in GOLD II patients and its prevalence progressively increased in GOLD III and IV patients. CONCLUSIONS: Most group O smokers exhibit increased phase III. With overt COPD there is a progressive increase in phase III and reduction of FEV(1)/FVC ratio from GOLD I to IV. A reduction of FEV(1) occurs from GOLD stage II. As the disease progresses from moderate to severe, there is an increasing presence of AC(T). Tidal EFL, with dynamic hyperinflation and severe dyspnea is present only in GOLD III and IV.